The objectives of this research proposal are: 1) to define the nature of the retinohypothalamic system responsible for the entrainment of self-sustaining circadian oscillators, 2) to describe all the afferent and efferent connections of the suprachiasmatic nucleus (SCN), 3) to examine the role of the internal coupling of the SCN in the expression of circadian rhythms, and 4) to determine the role of the serotonergic (5-HT) innervation of the SCN in the photoperiodic-gonadal response. The morphological characteristics of the retinal ganglion cells that innervate the SCN will be determined in retinal whole mounts in animals with bilateral optic tract lesions. HRP and 3H-amino acids will also be injected into the SCN to examine the afferent and efferent connections of this nucleus. Retinal synapses in the SCN in both photoperiodic and non-photoperiodic species will be examined by anterograde transport of HRP at the LM level. Studies employing HRP as an anterograde marker of retinal synapses in the SCN of the hamster will be conducted at the EM level. Studies employing two neuronal tracer molecules will be carried out to determine the site(s) of termination of collateral axonal branches of retinal ganglion cells that innervate SCN. Unilateral lesions of the SCN will be performed in hamsters that have displayed a dissociation of the circadian rhythms of locomotor activity into two components. Wheel running activity will be recorded with an event recorder before and after the neural ablation to determine the role of the internal coupling of the two SCN in the expression of circadian rhythms. The developmental plasticity of the retinohypothalamic tract will also be examined anatomically and behaviorally by performing unilateral enucleations in neonate hamsters. Additional studies using the neurotoxin 5,7-dihydroxytryptamine will be conducted. 5,7-DHT will be applied to the SCN to destroy the 5-HT terminals and then the animals response to both photo stimulatory and non-stimulatory light cycles will be examined to determine the role of 5-HT innervation of the SCN in the photoperiodic modulation of gonadotropin secretion.